Peterson alkenation elimination conditions

Mechanism The Peterson alkenation offers the synthesis of desired alkene stereoisomer by careful separation of the two diastereomeric intermediate P-hydroxysilanes and subsequently performing elimination under two different conditions. 

Boeckman and coworkers studied the reaction of bis(thmethylsilyl) ester (361) with aldehydes to form the silyl-substituted unsaturated ester (362 equation 86). The anion was formed with potassium or lithium diisopropylamide. Other metals, such as magnesium or aluminum, were introduce by treating the lithium anion with Lewis acids. The addition step produced a single diastereomer, en ling the effects of counterion and steric bulk on the elimination to be ascertained. Excellent selectivity for the ( )-isomer (362) may be obtained by using K or Li cations and a sterically hindered aldehyde. In studies directed toward the synthesis of substituted pseudomonic acid esters, the Peterson alkenation was utilized to form a mixture of (Z)- and ( )-alkene isomers, one example of which (365) is depicted in equation (87). In this example the conditions were optimized to form the highest degree of selectivity for the (Z)-alkene. 

Epoxide formation (path c) is an important side reaction which can become the dominant pathway. For example, the addition of sulfur ylides to ketones (equation 2) constitutes a general synthesis of epoxides, while 2-hydroxy sulfides undergo the semipinacol rearrangement under certain conditions (equation 3). Elimination (path d) is observed in some special cases such as 2-hydroxy si lanes (1 X = SiR.i the Peterson alkenation)" and 2-hydroxyphosphonium species (1 X = PRs" " Wittig intermediates). ... 

The transformation outlined in Scheme 14 nicely illustrates some of the advantages associated with the Peterson alkenation relative to the Homer-Emmons reaction for the conversion of the aldehyde (31) into the a,3-unsaturated aldehyde (32). When the corresponding phosphonate reagent is used, only the 3-hy-droxy phosphonate (33) is isolated elimination to form the a,3-unsaturated imine from (33) could not be induced under a variety of conditions. ... 

Synthesis of Vinyl Sulfides. Anion (2) adds to aldehydes, ketones, and enones, in the last-named case in either 1,2- or 1,4-manner depending on the reaction conditions.In the case of 1,2-addition the -hydroxysilane adduct usually cannot be isolated owing to rapid elimination (Peterson alkenation) to vinyl sulfides (eq 5), which can be hydrolyzed to the corresponding aldehydes. The vinyl sulfides are not formed stereoselectively unless there are proximate bulky substituents. Peterson alkenation products have also been observed in the reaction of (2) with amides, ureas, and carbonates. ... 

Peterson Alkenation. Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors. In some cases the use of (1) is superior to the Wittig approach. Condensation of (1) with a carbonyl compound results in the formation of a 8-hydroxysilane. Elimination to the alkene can be acconqtlished by use of acidic or basic conditions (eq 1). acetyl chloride or thionyl chloride can also be used to accomplish this elimination. A wide variety of aldehydes and ketones have been used as substrates in this reaction. The use of cerium(III) chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl corrqtounds. The use of the lithium agent (1) gives superior yields compared to the use of trimethylsilylmethyl-magnesium chloride with cerium, ... 

Peterson Alkenation. Trimethylsilylmethylmagnesium chloride (1) reacts with carbonyl compounds to give /3-hydroxysilanes (2).2>4,s silanes can then be eliminated to provide an alkene under acidic or basic conditions, such as with sodium hydride or potassium hydride (eq l).ia>ib,s,6 -pj g giinunation can also be accomplished by acetyl chloride or thionyl chloride. For the introduction of ex o-methylene groups, reagent (1) has been found to be superior to a Wittig approach the silicon reagent reacts rapidly and the byproduct is simple to remove. ... 

The Peterson olefination concerns the construction of double bonds from trialkylsilyl-substituted organometallics and carbonyls. The reaction involves the formation of an /ar-hydroxysilane, which then undergoes elimination to give the alkene. Elimination can take place under either acidic or basic conditions. 

The next step of the Peterson olefination allows for the control of the E Z-ratio of the alkene to be formed by proper choice of the reaction conditions. Treatment of /3-hydroxysilanes 5 with a base such as sodium hydride or potassium hydride leads to preferential -elimination to give alkene 3a as major... 

Y hen we discussed the Peterson reaction in Chapter 31, we explained that each diastereoisomer of a.P-silyl alcohol can eliminate, depending on the reaction conditions, to give either geometrical isomer of the alkene but we did not explain how these diastereoisomers could be made. This is how they are made. Elimination in base is a Wittig-style syn process but an anti elimination occurs in acid. Here are the reactions on one of the diastereoisomers we have just made. 

The first is a Wittig reaction with an unstabilized ylid, the second a Julia reaction, and the last two are Peterson reactions under different conditions. Each reaction is described in detail in the chapter. The Wittig reaction is under kinetic control and is a stereospecifically cis elimination. In this case the product is the Z-alkene. 

The Peterson reaction is a syn elimination under basic conditions, giving the Z-alkene, and an anti elimination under acidic conditions, giving the -alkene. 

As Peterson outlined in his preliminary communication of the method, either basic (KH, KOBu or NaH) or acidic conditions (acetic acid, sulfuric acid or boron trifluoride etherate) may be utilized to effect the elimination of the silylcarbinol. Alternatively the initial adduct may be treated in situ with thio-nyl or acetyl chloride. This procedure may be advantageous in cases where isomerization of the alkene is problematic, and is particularly useful in the synthesis of terminal alkenes. As discussed in Section 3.1.3.4.2, the Johnson group has successfully employed aqueous HF to effect the elimination and this method may also have advantages in situations complicated by base-catalyzed isomerization. ... 

The Peterson olefination is a connective alkene synthesis and represents a useful alternative to the Wittig reaction. The precursors for the Peterson olefination are 3-hydroxy-alkyltrimethylsilanes which undergo P-elimination of trimethylsilanol under basic or acidic conditions to furnish stereodefined alkenes. This olefination method is especially valuable for the preparation of terminal and exo-cyc ic double bonds and for the methylenation of hindered ketones where the Wittig reaction is problematic. Also, the... 

The exact pathway of the Peterson reaction is still not clear despite the intensive research effort. Most of the mechanistic studies suggest that both the stepwise and concerted pathways are feasible under basic conditions. In the concerted pathway a pentacoordinate 1,2-oxasiletanide is formed. The stepwise pathway is expected when chelation control operates in the reaction. The driving force is the formation of a very strong Si-0 bond. Under acidic conditions the 3-hydroxysilane undergoes an E2 elimination to afford the other alkene isomer. 

Conversion of the silane 12 to the alkene 13 can be accomplished by using a base such as KHMDS. Basic conditions promote syn elimination of p-hydroxysilanes (Peterson elimination, see Scheme 2.86). 

Similar to (chloromethyl)trimethylsilane, (chloromethyl)di-methylphenylsilane can be used to prepare alkenes via a Peterson olefination by treating C=0 compounds with Grignard 29. However, due to its propensity for rearrangements under the conditions needed for the elimination step, 1 appears less suited for this task than (chloromethyl)trimethylsilane if the silyl terminal alkenes are desired. However, in a parallel transformation, it was found that if the )3-silylalcohol 31 is treated with magnesium iodide etherate, then the Julia ring-opened homoallylation adduct 32 could be isolated (eq 15). ... 

Peterson went on to describe reactions of several lithiated silanes with carbonyls compounds, all giving the desired alkenes in good yields, albeit with very little stereoselectivity. In 1975 however, Peterson and Hudrlik published their studies on the stereoselective elimination of the hydroxyalkylsilyls. The reduction of 5-trimethylsilyl-4-octanone 10 was carried out with DIBAL-H to give one diastereoisomer, 11. The authors found that elimination with sodium or potassium hydride gave /ra 5-4-octene as the major isomer 12, while elimination under acidic conditions resulted in predominantly c/5-4-octene 13. Mild conditions were employed, affording stereochemical purity of up to 95% with excellent yields. 

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